Centre of Microbial and Plant Genetics, Katholieke Universiteit Leuven, Kasteelpark Arenberg 20, B-3001 Leuven, Belgium.
Bioorg Med Chem. 2010 Jul 15;18(14):5224-33. doi: 10.1016/j.bmc.2010.05.055. Epub 2010 May 25.
A library of 25 1'-unsubstituted and 1'-bromo or 1'-acetoxy 3-alkyl-5-methylene-2(5H)-furanones and two 3-alkylmaleic anhydrides was synthesized using existing and new methods. This library was tested for the antagonistic effect against the biofilm formation by Salmonella Typhimurium and the quorum sensing regulated bioluminescence of Vibrio harveyi. The length of the 3-alkyl chain and the bromination pattern of the ring structure were found to have a major effect on the biological activity of the 1'-unsubstituted furanones. Remarkably, the introduction of a bromine atom on the 1' position of the 3-alkyl chain did drastically enhance the activity of the furanones in both biological test systems. The introduction of an acetoxy function in this position did in general not improve the activity. Finally, the potential of the (bromo)alkylmaleic anhydrides as a new and chemically easily accessible class of biofilm and quorum sensing inhibitors was demonstrated.
使用现有和新方法合成了 25 个 1'-未取代和 1'-溴代或 1'-乙酰氧基 3-烷基-5-亚甲基-2(5H)-呋喃酮和两个 3-烷基马来酸酐。该文库用于测试对沙门氏菌生物膜形成的拮抗作用和群体感应调节的 Harveyi 弧菌生物发光。发现 3-烷基链的长度和环结构的溴化模式对 1'-未取代呋喃酮的生物活性有重大影响。值得注意的是，在 3-烷基链的 1'位置引入溴原子极大地增强了呋喃酮在这两个生物测试系统中的活性。在该位置引入乙酰氧基功能通常不会提高活性。最后，证明了（溴代）烷基马来酸酐作为一种新的、化学上易于获得的生物膜和群体感应抑制剂类别的潜力。
